Diabetes mellitus is characterized by insufficiency of the pancreatic β cells to maintain normal levels of blood glucose or normoglycemia. Under normal conditions, pancreatic β cells secrete insulin (as well as other hormones) in response to an increased blood glucose level, e.g., after a meal. Insulin acts to lower blood glucose levels through actions that include stimulation of fat synthesis, promotion of triglyceride storage in fat cells, and promotion of protein synthesis in the liver and muscle. In diabetes, the inability to maintain normoglycemia results from a failure of the pancreatic β cells to produce insulin, the development of insulin resistance in tissues that typically participate in blood glucose regulation, or some combination of these. The subsequent hyperglycemia contributes significantly to an increased risk of cardiovascular disease, neuropathy, nephropathy, retinopathy, hypertension, dyslipidemia, as well as increased morbidity and mortality.
In most patients with type I diabetes, pancreatic β cells are destroyed by an autoimmune response that can result in an absolute deficiency in insulin production. While some patients lack evidence of an autoimmune response against pancreatic β cells (known as idiopathic type 1 diabetics), the absence of pancreatic β cell still manifests itself as a deficiency in insulin production. Current treatments for type 1 diabetics include insulin injections as well as pancreatic β cell transplantation. Such therapies are risky and often unsuccessful. For example, it is difficult to regulate blood glucose with insulin rejections, and thus bouts of hypoglycemia are not uncommon. Insulin also frequently results in weight gain for the patient. Pancreatic islet transplantation carries all the risks associated with any organ transplantation which include side effects associated with the required immunosuppressive therapies to avoid transplant rejection. Finally, type I diabetes is most common is children and adolescents with an estimated 500,000 to 1 million type I diabetics in the United States alone.
Thus, it is urgent, unmet need for new methods of stimulating pancreatic β cell regeneration in the treatment of diabetes.